Plasmacytoid dendritic cells (pDC) are potent type I interferon (IFN-I) producing cells (Siegal et al., Science 284:1835 (1999)) and involved in controlling various viral infections (Cervantes-Barragan et al., Proc. Natl. Acad. Sci. USA 109:3012 (2012); Takagi et al., Immunity 35:958 (2011); Liu, Annu. Rev. Immunol. 23:275 (2005); Swiecki et al., Immunity 33:955 (2010)). However, the contribution of pDC in human immunodeficiency virus-1 (HIV-1) infection and pathogenesis remains controversial. On one hand, pDC have been shown to inhibit HIV-1 replication through IFN-1 production (Yonezawa et al., J. Virol. 77:3777 (2003); Fong et al., J. Virol. 76:11033 (2002); Gurney et al., J. Immunol. 173:7269 (2004)). Moreover, the numerical and functional decline of pDC in HIV-1 infected patients correlates with opportunistic infection independent of CD4+ T-cell counts (Siegal et al., J. Clin. Invest. 78:115 (1986); Feldman et al., Clin. Immunol. 101:201 (2001); Lichtner et al., Curr. HIV Res. 6:19 (2008)). On the other hand, pDC may contribute to HIV immunopathogenesis. The sustained pDC activation and IFN-1 production in HIV-1 infected patients does not correlate with viral control but is predictive of disease progression (Buimovici-Klein et al., Lancer 2:344 (1983); Buimovici-Klein et al., AIDS Res. 2:99-108 (1986); Meier et al., Nature Medicine 15:955 (2009)). Additionally, pDC are activated during the acute phase of simian immunodeficiency virus (SIV) infection in both pathogenic Asian monkeys (Rhesus and cynomolgus macaques) and non-pathogenic African monkeys (Sooty mangabeys and African green monkeys). However, pDC activation is rapidly controlled in the nonpathogenic SIV infection, whereas its activation and IFN-I production are sustained during pathogenic infection in Asian monkey (Lederer et al., PLoS Pathogens 5:e1000296 (2009); Bosinger et al., J. Clin. Invest. 19:3556 (2009); Jacquelin et al., J. Clin. Invest. 119:3544 (2009); Harris et al., J. Virol. 84:7886 (2010); Campillo-Gimenez et al., J. Virol. 84:1838 (2010)). Thus, the interaction between HIV and pDCs is unclear.
The present invention addresses previous shortcomings in the art by providing antibodies that deplete pDC in a subject and treat disorders associated with pDC.